skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Steps toward the generation of ovarian somatic cells from pluripotent stem cells
The generation of functional gametes, both eggs and sperm, from murine pluripotent stem cell (PSC) sources, has set the stage for the eventual use of this emerging technology in other species. With the field enthusiastically embracing this eventuality, in particular for animal conservation efforts, there are a number of key factors to consider regarding the applicability of these methods across species, particularly with regard to the generation of eggs. To date, published studies point to the need for fetal somatic tissue and primitive granulosa cells to serve as a niche for the growth and maturation of oocytes generated from PSCs. In practice, the need for such tissue represents a major limitation when attempting to apply this to species in which access to fetal ovaries is limited or unethical. To circumvent this, we and others have derived methods to generate ovarian granulosa cells from PSCs, albeit with low yield. Herein we present an update on the status of generating early stage granulosa cells from PSCs, and provide evidence for improvements based on a stepwise, 2-dimensional protocol for the directed differentiation of human PSCs.  more » « less
Award ID(s):
1750996
PAR ID:
10310210
Author(s) / Creator(s):
;
Date Published:
Journal Name:
Clinical Theriogenology Journal
Volume:
12
Issue:
4
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Progenitor cells isolated from the fetal liver can provide a unique cell source to generate new healthy tissue mass. Almost 20 years ago, it was demonstrated that rat fetal liver cells repopulate the normal host liver environment via a mechanism akin to cell competition. Activin A, which is produced by hepatocytes, was identified as an important player during cell competition. Because of reduced activin receptor expression, highly proliferative fetal liver stem/progenitor cells are resistant to activin A and therefore exhibit a growth advantage compared to hepatocytes. As a result, transplanted fetal liver cells are capable of repopulating normal livers. Important for cell-based therapies, hepatic stem/progenitor cells containing repopulation potential can be separated from fetal hematopoietic cells using the cell surface marker δ-like 1 (Dlk-1). In livers with advanced fibrosis, fetal epithelial stem/progenitor cells differentiate into functional hepatic cells and out-compete injured endogenous hepatocytes, which cause anti-fibrotic effects. Although fetal liver cells efficiently repopulate the liver, they will likely not be used for human cell transplantation. Thus, utilizing the underlying mechanism of repopulation and developed methods to produce similar growth-advantaged cells in vitro, e.g., human induced pluripotent stem cells (iPSCs), this approach has great potential for developing novel cell-based therapies in patients with liver disease. The present review gives a brief overview of the classic cell transplantation models and various cell sources studied as donor cell candidates. The advantages of fetal liver-derived stem/progenitor cells are discussed, as well as the mechanism of liver repopulation. Moreover, this article reviews the potential of in vitro developed synthetic human fetal livers from iPSCs and their therapeutic benefits. 
    more » « less
  2. Jeffrey, Peters; Alison, Harrill; Kristine, Willett (Ed.)
    Phthalates are a class of known endocrine-disrupting chemicals that are found in common everyday products. Several studies associate phthalate exposure with detrimental effects on ovarian function, including growth and development of the follicle and production of steroid hormones. We hypothesized that dysregulation of the ovary by phthalates may be mediated by phthalate toxicity towards granulosa cells, a major cell type in ovarian follicles responsible for key steps of hormone production and nourishing the developing oocyte. To test the hypothesis that phthalates target granulosa cells, we harvested granulosa cells from adult CD-1 mouse ovaries and cultured them for 96 h in vehicle control, a phthalate mixture, or a phthalate metabolite mixture (0.1 to 100 μg/ml). After culture, we measured metabolism of the phthalate mixture into monoester metabolites by the granulosa cells, finding that granulosa cells do not significantly contribute to ovarian metabolism of phthalates. Immunohistochemistry of phthalate metabolizing enzymes in whole ovaries confirmed that these enzymes are not strongly expressed in granulosa cells of antral follicles and that ovarian metabolism of phthalates likely occurs primarily in the stroma. RNA sequencing of treated granulosa cells identified 407 differentially expressed genes, with overrepresentation of genes from lipid metabolic processes, cholesterol metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Expression of significantly differentially expressed genes related to these pathways was confirmed using qPCR. Our results agree with previous findings that phthalates and phthalate metabolites have different effects on the ovary, but both interfere with PPAR signaling in granulosa cells. 
    more » « less
  3. Perovskites have been firmly established as one of the most promising materials for third-generation solar cells. There remain several great and lingering challenges to be addressed regarding device efficiency and stability. The photovoltaic efficiency of perovskite solar cells (PSCs) depends drastically on the charge-carrier dynamics. This complex process includes charge-carrier generation, extraction, transport and collection, each of which needs to be modulated in a favorable manner to achieve high performance. Two-dimensional materials (TDMs) including graphene and its derivatives, transition metal dichalcogenides ( e.g. , MoS 2 , WS 2 ), black phosphorus (BP), metal nanosheets and two-dimensional (2D) perovskite active layers have attracted much attention for application in perovskite solar cells due to their high carrier mobility and tunable work function properties which greatly impact the charge carrier dynamics of PSCs. To date, significant advances have been achieved in the field of TDM-based PSCs. In this review, the recent progress in the development and application of TDMs ( i.e. , graphene, graphdiyne, transition metal dichalcogenides, BP, and others) as electrodes, hole transporting layers, electron transporting layers and buffer layers in PSCs is detailed. 2D perovskites as active absorber materials in PSCs are also summarized. The effect of TDMs and 2D perovskites on the charge carrier dynamics of PSCs is discussed to provide a comprehensive understanding of their optoelectronic processes. The challenges facing the PSC devices are emphasized with corresponding solutions to these problems provided with the overall goal of improving the efficiency and stability of photovoltaic devices. 
    more » « less
  4. Abstract Placentation evolved many times independently in vertebrates. While the core functions of all placentas are similar, we know less about how this similarity extends to the molecular level. Here we study Poeciliopsis, a unique genus of live-bearing fish that have independently evolved complex placental structures at least three times. The maternal follicle is a key component of these structures. It envelops yolk rich eggs and is morphologically simple in lecithotrophic species, but has elaborate villous structures in matrotrophic species. Through sequencing the follicle transcriptome of a matrotrophic, P. retropinna, and lecithotrophic, P. turrubarensis, species we found genes known to be critical for placenta function expressed in both species despite their difference in complexity. Additionally, when we compare the transcriptome of different river populations of P. retropinna, known to vary in maternal provisioning, we find differential expression of secretory genes expressed specifically in the top layer of villi cells in the maternal follicle. This provides some of the first evidence that the placental structures of Poeciliopsis function using a secretory mechanism rather than direct contact with maternal circulation. Finally, when we look at the expression of placenta proteins at the maternal-fetal interface of a larger sampling of Poeciliopsis species, we find expression of key maternal and fetal placenta proteins in their cognate tissue types of all species, but follicle expression of Prolactin is restricted to only matrotrophic species. Taken together, we suggest that all Poeciliopsis follicles are poised for placenta function, but require expression of key genes to form secretory villi. 
    more » « less
  5. Abstract Polymer solar cells (PSCs) with a bulk heterojunction (BHJ) device structure have incredible advantages, such as low‐cost fabrication and flexibility. However, the power conversion efficiency (PCE) of BHJ PSCs needs to be further improved to realize their practical applications. In this study, boosted PCEs from PSCs based on BHJ composites incorporated with Fe3O4magnetic nanoparticles (MNPs), aligned by an external magnetic field (EMF), are reported. It is found that the coercive electric field within the Fe3O4MNPs generated by the EMF has a strong and positive influence on the charge generation, which results in a more than 10% increase in free charge carriers. Moreover, the coercive electric field speeds up the charge carrier transport and suppresses charge carrier recombination within PSCs. In addition, a shortened extraction time makes charge carriers more likely to make it to the electrodes. As a result, more than 15% enhancement in PCE is observed from the PSCs based on the BHJ composite incorporated with the Fe3O4MNPs and the EMF as compared with that based on the BHJ composite thin film. This work indicates that the incorporation of MNPs and the EMF is a facile way to enhance the PCEs of PSCs. 
    more » « less